Biomedical subjects

L K Toivonen

Publications and source records attributed to L K Toivonen.

At least 19 recordsLinked to original sources

PubMed1999

Acute effects of intravenous magnesium on ventricular refractoriness and monophasic action potential duration in humans.

The objective of this study was to examine the antiarrhythmic mechanisms of magnesium (Mg). The 12 patients who were selected for the study were given 12 mmol Mg sulphate followed by an infusion of 8 mmol/h. Ventricular effective refractory period (VERP). monophasic action potential duration at 50% and 90% repolarization during spontaneous rhythm (MAPD50, MAPD90) and atrial pacing at a cycle length of 600 ms (MAPD(50)600, MAPD(90)600) were measured before and after the intervention. Plasma magnesium concentration rose from 0.83 +/- 0.05 to 1.85 +/- 0.24 mmol/l (p < 0.001). Shortening of MAPD(50) (250 +/- 45 vs 240 +/- 46 ms; p < 0.05), MAPD(90) (294 +/- 42 vs 283 +/- 41 ms; p < 0.05) and shortening of sinus cycle length (SCL) (783 +/- 153 vs 742 +/- 160 ms; p < 0.01) were detected. During controlled cycle length, magnesium decreased MAPD(50)600 (230 +/- 28 vs 221 +/- 28 ms; p < 0.01), MAPD(90)600 (274 +/- 25 vs 261 +/- 29 ms; p < 0.01) and VERP (247 +/- 25 vs 241 +/- 21 ms: p < 0.05). QRS duration, QT interval and blood pressure remained unchanged. The change in SCL correlated with the change in MAPD(50) (r = 0.58; p < 0.05) and MAPD(90) (r = 0.55; p = 0.06 ) but not with MAPD(50)600, MAPD(90)600 or VERP. Magnesium acutely shortens ventricular monophasic action potential duration and refractoriness. This effect is partly mediated by mechanisms that increase heart rate. The reductions might bring salutary effects in arrhythmias evoked by prolonged repolarization.

Action Potentials↗

PubMed1990

The ventricular excitability-interval relationship in early diastole in humans: the influence of the electrode configuration during bipolar stimulation.

The purpose of this study was to determine the relationship between ventricular excitability and the extrastimulus (S2) coupling interval in early diastole in humans. The influence of the electrode configuration during bipolar stimulation was examined. Ventricular strength-interval curves were constructed using an eight beat drive train at a cycle length of 600 msec, 2-msec decrements in the S2 coupling interval, and 0.2-mA increments in the current intensity of S2 at each coupling interval. A transient dip in the excitation threshold was observed in early diastole during bipolar pacing when the distal electrode was the anode in six of 17 patients (35%). In contrast, this type of dip was not observed when the distal electrode was the cathode. The excitation threshold at the trough of the dip ranged from 1.0 to 2.2 mA. Unipolar strength-interval curves indicated that a dip occurred with anodal but not cathodal pacing. We postulated that the dip might interfere with the accurate determination of the ventricular effective refractory period by resulting in transient loss of ventricular capture during decremental scanning of diastole with S2. A gap in ventricular capture was produced in all six patients who demonstrated a dip in the bipolar strength-interval curve by selecting an S2 current intensity that fell within the dip. In conclusion, the bipolar strength-interval curve may display an early diastolic dip in the excitation threshold, depending on the electrode configuration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗

PubMed1989

Comparison of ventricular refractory periods determined by incremental and decremental scanning of an extrastimulus.

This study compared the ventricular effective refractory periods measured by scanning diastole with an extrastimulus in incremental and decremental steps of 5 msec. The subjects of the study were 80 patients undergoing a clinically indicated electrophysiological test. Eight beat basic drive trains at a cycle length of 600 msec and an intertrain pause of 4 seconds were used to measure the ventricular effective refractory period (VERP). In the incremental method, the extrastimulus initially was positioned at a coupling interval shorter than the VERP and the coupling interval then was progressively increased until ventricular capture occurred. In the decremental method, the initial extrastimulus coupling interval was longer than the VERP and the coupling interval was progressively shortened until ventricular capture was lost. In 50 subjects, the mean VERP determined by the incremental method, 252 +/- 18 (+/- standard deviation), was significantly longer than the mean VERP determined in the same patients by the decremental method, 248 +/- 18 msec (P less than 0.0001). In ten subjects, a subthreshold stimulus (S') positioned 10 msec earlier than the VERP had an inhibitory effect that lengthened the VERP by an average of 7 msec; however, when S' was positioned after the seventh beat of an eight beat drive train, no inhibitory effect could be demonstrated. In 20 subjects, VERP's were determined by the incremental and decremental methods using intertrain pauses of 1, 4, 8, 12, and 20 seconds.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗

PubMed1989

Epinephrine-induced reversal of verapamil's electrophysiologic and therapeutic effects in patients with paroxysmal supraventricular tachycardia.

The purpose of our study was to determine whether an infusion of epinephrine reverses the electrophysiologic effects of verapamil and whether reversal of verapamil's effects on the induction of paroxysmal supraventricular tachycardia (PSVT) by epinephrine during electropharmacologic testing is predictive of stress-related recurrences of PSVT during long-term treatment with verapamil. The infusion rates of epinephrine used in this study were 25 and 50 ng/kg/min, which previously have been demonstrated to result in plasma epinephrine concentrations in the range that occurs during a variety of stresses in humans. The subjects of this study were 17 patients with recurrent PSVT who underwent an electrophysiologic study in the control state and after at least 2 days of treatment with 240-480 mg/day verapamil. After assessing the response to verapamil, epinephrine was infused and testing was repeated. Verapamil significantly slowed atrioventricular conduction and prolonged refractoriness in the atrium and atrioventricular node. The effects of the two infusion rates of epinephrine were generally similar in magnitude and, therefore, the results were pooled. Epinephrine partially or completely reversed all of verapamil's electrophysiologic effects. Verapamil suppressed the induction of sustained PSVT in 15 patients. Epinephrine facilitated the induction of PSVT in seven of these 15 patients. All 15 patients were treated on a long-term basis with verapamil. The eight patients in whom epinephrine did not facilitate the induction of PSVT had no recurrences of PSVT during 9-18 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol↗

PubMed1988

Effects of epinephrine in patients with an accessory atrioventricular connection treated with quinidine.

The purpose of this study was to determine whether physiologic doses of epinephrine reverse the electrophysiologic effects of quinidine in patients with an accessory atrioventricular (AV) connection. Eighteen patients with an accessory AV connection who had inducible sustained orthodromic tachycardia underwent an electrophysiologic study in the baseline state and after at least 2 days of treatment with 1.4 to 1.9 g/day of quinidine gluconate. The effects of epinephrine were then determined. Epinephrine infusion rates of 25 and 50 ng/kg/min were used in 9 patients each because these doses of epinephrine previously have been demonstrated to result in elevated plasma epinephrine concentrations in the range that occurs during a variety of stresses in humans. Quinidine prolonged refractoriness in the atrium and accessory AV connection and slowed conduction through the accessory AV connection. These effects were partially or completely reversed by epinephrine. Among 8 patients in whom quinidine resulted in orthodromic tachycardia becoming noninducible or nonsustained, sustained tachycardia became inducible again in 5 patients after infusion of epinephrine. After quinidine, atrial fibrillation was either noninducible or nonsustained in 8 patients; however, sustained atrial fibrillation could be induced in 4 of these patients after infusion of epinephrine. The results of this study demonstrate that the therapeutic effect of quinidine in patients who have an accessory AV connection are often reversed by physiologic increases in circulating epinephrine.

Adult↗

PubMed1988

Antagonism of quinidine's electrophysiologic effects by epinephrine in patients with ventricular tachycardia.

The purpose of this study was to determine whether pharmacologically induced elevations in the plasma epinephrine concentration within reported physiologic limits alter the response to quinidine during electropharmacologic testing. Twenty-one patients with coronary artery disease and a history of unimorphic ventricular tachycardia were found to have inducible sustained unimorphic ventricular tachycardia that was suppressed by treatment with oral quinidine gluconate. Epinephrine was then infused at a rate of either 25 or 50 ng/kg per min and testing was repeated. These infusion rates of epinephrine were previously demonstrated to result in elevations of the plasma epinephrine concentration in the range of concentrations that occur during a variety of stresses. Quinidine significantly lengthened the ventricular refractory periods and the QRS duration at a ventricular pacing cycle length of 350 ms, which was used as an index of intraventricular conduction. Epinephrine partially or completely reversed the effects of quinidine on ventricular refractory periods, but had no effect on QRS duration. During electropharmacologic testing of quinidine, no ventricular tachycardia was inducible in 12 patients, and only nonsustained ventricular tachycardia, 8 to 48 beats in duration, was inducible in 9 patients. Retesting during infusion of epinephrine demonstrated inducible sustained unimorphic ventricular tachycardia in 2 of the 12 patients in whom quinidine had completely suppressed the induction of ventricular tachycardia and in 8 of the 9 patients in whom only nonsustained ventricular tachycardia had been inducible during testing of quinidine. In conclusion, physiologic elevations in the plasma epinephrine concentration may reverse quinidine-induced prolongation of ventricular refractoriness but not intraventricular conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

The maximum effect of an increase in rate on human ventricular refractoriness.

The purpose of this study was to determine the maximum shortening of ventricular refractoriness that occurs following an increase in rate and to quantitate the duration of ventricular pacing required to obtain this maximum shortening of refractoriness. The subjects of the study consisted of 41 patients who underwent a clinically indicated electrophysiologic study. Ventricular refractory periods were measured with an extrastimulus (S2) at basic cycle lengths of 600 and 400 ms by Method A (8 beat basic drive trains and 4 second intertrain paue and Method B (drive train duration of 3 minutes, then an S2 after every eighth basic drive beat, with no pause after the S2). In 23 subjects, the mean ventricular effective refractory period determined by Method B was 12 +/- 7 ms (+/- standard deviation) shorter than when determined by Method A at a basic drive cycle length of 600 ms (p less than 0.0001) and 33 +/- 9 ms shorter at a basic drive cycle length of 400 ms (p less than 0.001). In these 23 subjects, the drive train duration required for maximum shortening of ventricular refractoriness was estimated by counting the number of drive train beats preceding ventricular capture by an S2 inserted after every fourth basic drive beat at a coupling interval fixed at 5 ms longer than the ventricular effective refractory period determined in that subject by Method B. The mean number of basic drive beats preceding capture by S2 was 114 +/- 84 beats at a basic drive cycle length of 600 ms and 233 +/- 85 beats at a BDCL of 400 ms. In six subjects the ventricular effective refractory period was measured by Methods A and B before and after autonomic blockade with propranolol and atropine, and the amount of shortening in the ventricular effective refractory period with Method B was not affected by autonomic blockade. In conclusion, the basic drive train has a cumulative effect on ventricular refractoriness in humans, and a drive train duration substantially longer than 50 beats often is required to obtain the maximum shortening of ventricular effective refractory period after an increase in rate. Therefore, ventricular effective refractory periods determined conventionally using 8 beat drive trains and a 4 second intertrain pause often may be overestimates of the actual ventricular effective refractory period. The shortening of ventricular refractoriness with long drive train durations is probably related to a prolonged duration of pacing required to obtain a steady-state action potential duration after an increase in rate.

Action Potentials↗

PubMed1988

Accentuated antagonism between beta-adrenergic and vagal effects on ventricular refractoriness in humans.

The purpose of this study was to determine whether there is accentuated antagonism between sympathetic and vagal effects on ventricular refractory periods (VRPs) in humans. The effects of 0.04 mg/kg of atropine on the right ventricular effective and functional refractory periods were determined in the setting of beta-adrenergic blockade by propranolol (0.15 mg/kg loading dose, then 0.1 mg/min continuous infusion, group 1) and in the setting of beta-adrenergic stimulation by 25 or 50 ng/kg/min isoproterenol (groups 2 and 3, respectively). Groups 4 to 6 served as control groups. In group 4, VRPs were determined on three occasions separated by 10 min each in the absence of drug. VRPs also were determined on two occasions after infusion of propranolol (group 5) or 25 ng/kg/min of isoproterenol (group 6). Groups 1 to 4 consisted of 10 subjects each, and groups 5 and 6 consisted of five subjects each. VRPs were determined with the use of basic drive cycle lengths of 600, 500, 400, and 350 msec. Because of sinus tachycardia, sufficient data for comparison of groups 1 to 3 were available only at drive cycle lengths of 400 and 350 msec. Atropine significantly shortened the VRPs in groups 1 to 3, but the magnitude of atropine's effects in group 3 (5.3% to 5.8% shortening at drive cycle length of 350 msec) was significantly greater than in group 1 (2.6% to 3.0% shortening, p less than .05) Data from the control groups demonstrated that there was no effect of time on measurement of VRPs either in the drug-free state or in the presence of propranolol or isoproterenol. The results of this study indicate that cholinergic tone lengthens VRPs in the absence of background sympathetic activity and that this lengthening of VRPs may become accentuated during beta-adrenergic stimulation.

Adult↗

PubMed1987

Pirmenol in the termination of paroxysmal supraventricular tachycardia.

The effects of pirmenol in terminating paroxysmal supraventricular tachycardia were studied in 25 patients. Pirmenol was administered as 1 or 2 injections of 50 mg to 17 patients during a spontaneous attack, or as a 50-mg bolus followed by steady infusion of 2.5 mg/min in 8 patients during a tachycardia that was induced electrophysiologically. Termination was successful in 11 of 17 patients who had a spontaneous attack and in 3 of 8 patients who had induced tachycardia. Pirmenol was effective in 3 of 5 patients with atrioventricular nodal reentrant mechanism, but in none of 3 patients with a reentrant tachycardia with a retrogradely conducting atrioventricular bypass tract. Conversion to sinus rhythm was achieved in 14 of 25 patients (56%). No hemodynamic adverse effects occurred. Pirmenol increased the atrial effective refractory period, but had little effect on conduction in the atrioventricular node and His-Purkinje system. Reentry was abolished through a block in the retrograde part of the dual atrioventricular nodal pathway, which is typical of class I antiarrhythmic agents.

Adolescent↗

PubMed1987

Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol.

The acute effects of pirmenol on atrial fibrillation were investigated in 40 patients with paroxysm of atrial fibrillation. Patients were randomized to receive either pirmenol, 50 or 100 mg intravenously, or placebo. Patients with congestive heart failure or a history of sinus node disorder were excluded. Sinus rhythm was achieved in 12 of 20 patients in 2 to 16 minutes after pirmenol administration and in 3 of 20 patients in the control group within 1 hour. A nodal escape rhythm during sinus slowing was observed in 1 patient. No sinus arrest, atrioventricular conduction disturbance or hypotension appeared. Pirmenol has an antifibrillatory effect on the atria. Sinus rhythm is restored rapidly after intravenous administration. Treatment of atrial fibrillation of recent onset was well tolerated in patients accepted for the study.

Adrenergic beta-Antagonists↗

PubMed1987

Vasodilator therapy-induced pacemaker syndrome.

Disabling presyncopal attacks were provoked in a patient with a sinus nodal disorder and cardiac pacemaker by treatment with antianginal vasodilators. At cardiac catheterization a severe fall in aortic pressure was documented during ventricular pacing, when desynchronized atrial contractions coincided with ventricular systoles. After withdrawal of the medication, no obvious changes in arterial pressure were associated with ventricular pacing, and the patient became free of dizziness. Vasodilating drugs may provoke episodic hypotension with characteristic features of the pacemaker syndrome.

Humans↗

PubMed1986

Pirmenol in termination of paroxysmal supraventricular tachycardia.

An assessment was made of the effect of pirmenol in the termination of paroxysmal supraventricular tachycardia (SVT). Sinus rhythm was restored by intravenous administration in 11 of 17 patients during a spontaneous attack. Another 8 patients were studied electrophysiologically. Pirmenol terminated an induced SVT in 3 of 5 patients having an atrioventricular (AV) intranodal re-entry mechanism but in none of 3 patients having an atrioventricular bypass tract as one re-entrant limb. The overall success in restoring sinus rhythm was 14 of 25 patients (56%). The drug was hemodynamically well tolerated even in cases of continued SVT. Pirmenol increased the atrial effective refractory period and had no obvious effect on AH and HV intervals. The functional refractory period of the AV node was decreased, probably by an anticholinergic effect. The effective and functional refractory periods of retrograde atrioventricular conduction via the AV node and bypass tract were increased in some patients. The mechanism terminating the AV intranodal SVT was a block in the retrograde part of the dual AV nodal pathway, a typical antiarrhythmic Class I effect.

Adolescent↗

PubMed1986

Hemodynamic effects of pirmenol, a new antiarrhythmic agent, assessed noninvasively.

The cardiovascular effects of a new antiarrhythmic Class I agent, pirmenol, were assessed noninvasively in 10 patients without heart failure. Infusion of 100 mg pirmenol was given over 30 min following baseline M-mode echocardiography, cuff blood pressure and systolic time interval measurements. The measurements were repeated after the infusion, and 15 and 60 min later. Heart rate increased by 14.7% (P less than 0.01). Significant increases were also noted in afterload parameters, mean arterial pressure (+10.1%; P less than 0.001) and mid-systolic left ventricular wall stress (+8.0%; P less than 0.05). Concomitantly a slight increase was observed in preload, reflected in lengthening of left ventricular end-diastolic diameter (+4.8%; P less than 0.05). A decrease in fractional shortening (-6.5%; P less than 0.05) and an increase in pre-ejection period/left ventricular ejection time ratio (+16.2%; P less than 0.01) suggested a negative inotropic effect. The increased afterload and heart rate may have contributed to changes in these indices, and therefore myocardial depression may appear more pronounced than it actually was. The main effects of intravenous administration of pirmenol are elevations in heart rate and blood pressure. The induced decrease in myocardial contractility is slight.

Adult↗

PubMed1986

Limited effect of magnesium sulphate on torsades de pointes ventricular tachycardia.

A patient with thioridazine-induced torsades de pointes ventricular tachycardia treated with magnesium sulphate is presented. Due to incessant recurrence of tachycardias it was possible to observe the time course of the effect of 1 g intravenous doses. Suppression of torsades de pointes lasted at best for no more than 18 min and a maintenance infusion was not effective without overdrive pacing. Magnesium sulphate may have value as first aid therapy for drug-induced torsades de pointes ventricular tachycardia. However, its effect disappears rapidly, and, therefore, should not alone be relied on as prophylactic treatment.

Electrocardiography↗

PubMed1986

Acute haemodynamic effects of the antiarrhythmic agent pirmenol in cardiac patients: a comparison with lidocaine.

The acute haemodynamic effects of pirmenol, a new Class 1 antiarrhythmic agent, were investigated in a double-blind comparison with lidocaine and placebo. Three groups of 10 patients each received either pirmenol as a 50 mg intravenous injection followed by a 2.5 mg min-1 infusion, or lidocaine as a 75 mg injection followed by a 3 mg min-1 infusion, or placebo. Mean plasma pirmenol concentrations during the 30 min infusion period were 2.3-2.5 mg l-1, and were considered to be therapeutically effective. Compared to measurements taken during a baseline phase of 15 min duration, pirmenol increased heart rate by 10 beats min-1 (P less than 0.001) and mean arterial pressure (MAP) by 5 mmHg (P less than 0.001). It also increased systemic vascular (P less than 0.05) and pulmonary arterial resistances (P less than 0.01). Left ventricular end-diastolic pressure (LVEDP) was not increased significantly. Cardiac index and left ventricular work index remained unchanged. Lidocaine induced a comparable increase in MAP (6 mmHg; P less than 0.001) and elevated LVEDP (2.8 mmHg; P less than 0.05) and did not affect left ventricular work index. Echocardiographic left ventricular ejection fraction was reduced more by pirmenol (-0.05; P less than 0.001) than by lidocaine (-0.03; P less than 0.05), but the greater reduction may partly be explained by the increase in heart rate. Primenol did not induce excessive circulatory responses or side-effects in any patient. Intravenous administration of pirmenol results in increased heart rate and afterload but has little effect on preload. The myocardial depressant effect is relatively slight, and comparable to that of lidocaine.

Adult↗

PubMed1986

Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol. A placebo controlled study.

The efficacy of pirmenol (a class I antiarrhythmic agent) as a converter of paroxysmal atrial fibrillation was investigated. Forty patients without congestive heart failure or a history of sinus node disorder were randomly allocated to receive either intravenous pirmenol (50-100 mg) or placebo in a double blind trial. In 12 of 20 patients sinus rhythm was restored 2-16 minutes after pirmenol, and in 3 of 20 patients in the control group it returned within one hour. A nodal escape rhythm was seen during sinus slowing in one patient, but in other patients there was no sinus arrest, atrioventricular conduction disturbance, or hypotension. The ventricular rate was slightly increased in patients in whom sinus rhythm was not restored by pirmenol. The results indicate that pirmenol has an antifibrillatory effect on the atria. Sinus rhythm was restored rapidly after intravenous administration. It was well tolerated in patients with atrial fibrillation of recent onset.

Anti-Arrhythmia Agents↗

PubMed1986

Effect of pirmenol on premature atrial complexes.

Suppression of premature atrial complexes by pirmenol, a new Class I antiarrhythmic agent, was examined following oral and intravenous routes of administration. In 4 patients, single intravenous doses of 50 to 150 mg reduced premature atrial beats greater than or equal to 90% for 2 to 4 h. Oral doses of 75 to 200 mg twice daily induced a mean arrhythmia reduction of greater than or equal to 80% in 5 out of 9 patients during a 24-h electrocardiographic recording compared with a baseline period of 48 h. No significant side-effects occurred. The results indicate that pirmenol effectively suppresses premature atrial complexes, which may be of value in the prevention of supraventricular tachyarrhythmias.

Administration, Oral↗

PubMed1985

Antiarrhythmic efficacy of pirmenol in the treatment of premature ventricular complexes.

We assessed the antiarrhythmic effectiveness, therapeutic plasma concentrations and adverse effects of pirmenol in 16 patients with frequent (mean 933 h-1) premature ventricular complexes (PVC). Progressive increase in dose to a maximum of 200 mg twice daily suppressed PVC in a majority of patients. By preset criteria 11 patients (69%) exhibited an effective suppression of PVCs whereas in 5 patients (31%) the suppression was inadequate despite therapeutic plasma concentrations. The responders exhibited an 87% mean reduction of PVCs and a 97% reduction in repetitive PVC. This therapeutic effectiveness was verified against placebo by repetitive 24-hour ECG monitorings recorded in a double-blind cross-over fashion. The plasma trough concentration during the effective dose averaged 1.31 +/- 0.67 mg-1 (SD). The efficacy was maintained with the twice daily regimen despite an elimination half life of 6.3 +/- 1.7 h (SD) but a slight decrease in PVC suppression was observed towards the end of the administration interval. Pirmenol was well tolerated but aggravation of the arrhythmia occurred in one patient who shared an associated excessive prolongation of the Q-T interval, a feature observed with quinidine-like class I agents.

Anti-Arrhythmia Agents↗